Bruton's tyrosine kinase targets NF-κB to the bcl-x promoter via a mechanism involving phospholipase C-γ2 following B cell antigen receptor engagement

James B. Petro, Iris Castro, John Lowe, Wasif N. Khan

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Disruption of Bruton's tyrosine kinase (BTK) function leads to x-linked immunodeficiency (xid) in mice. BTK-deficient (btk-/-) B cells are defective for survival. Prior studies show that BTK is required for the induction of Bcl-xL following B cell antigen receptor (BCR) engagement. However, the mechanism underlying Bcl-xL induction in response to BCR ligation remains unresolved. We now demonstrate that BTK regulates bcl-x expression by transcriptional control in response to BCR engagement. BTK targets nuclear factor-κB (NF-κB) to activate the bcl-x promoter via a phospholipase C-γ2 (PLC-γ2)-dependent mechanism. Perturbation of the BTK/PLC-γ2/NF-κB signaling axis likely contributes to the defective expression of bcl-x and compromised survival of xid B cells.

Original languageEnglish (US)
Pages (from-to)57-60
Number of pages4
JournalFEBS letters
Volume532
Issue number1-2
DOIs
StatePublished - Dec 4 2002
Externally publishedYes

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Keywords

  • B cell antigen receptor
  • Bcl-x
  • Bruton's tyrosine kinase
  • Nuclear factor-κB
  • Phospholipase C-γ2
  • X-linked immunodeficiency

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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